TY - JOUR
T1 - CASZ1 is a novel promoter of metastasis in ovarian cancer
AU - Wu, Yi Ying
AU - Chang, Chia Lin
AU - Chuang, Yuan Jhe
AU - Wu, Jia En
AU - Tung, Chia Hao
AU - Chen, Yeong Chang
AU - Chen, Yuh Ling
AU - Hong, Tse Ming
AU - Hsu, Keng Fu
N1 - Funding Information:
We are grateful for the services provided by the RNAi Core Lab and the support from the Human Biobank, the Research Center of Clinical Medicine, and the National Cheng Kung University Hospital, Taiwan. RNAi reagents were obtained from the National RNAi Core Facility located at the Institute of Molecular Biology/Genomic Research Center, Academia Sinica, Taiwan. This study was supported by the following grants: NSC 102-2314-B-006-049-MY2 and MOST 104-2314-B-006-072-MY2 from the Ministry of Science and Technology, Taiwan; and NCKUH-10407015 from the National Cheng Kung University Hospital, Taiwan.
PY - 2016
Y1 - 2016
N2 - Epithelial ovarian cancer (EOC) carries the highest mortality rate of all gynecologic malignancies. This high mortality rate is attributed to the fact that most cases of ovarian cancer are detected at late stages when metastases are already present. Through microarray analysis, we previously demonstrated that castor zinc finger 1 (CASZ1) is up-regulated in EOC cells. In contrast to its role in EOC, CASZ1 functions a tumor suppressor in neuroblastoma. Human CASZ1 is predominantly expressed in 2 alternatively spliced isoforms: CASZ1a and CASZ1b. In the present study, we investigated the role of CASZ1 in ovarian cancer cell migration and invasion and assessed the value of CASZ1 expression as a prognostic indicator of metastasis in human ovarian cancer. We used a lentivirus expressing CASZ1-shRNA and a plasmid expressing CASZ1 from a CMV promoter to knockdown and overexpress CASZ1, respectively, in the MCAS, RMUG-S, TOV21G, and A2780CP70 ovarian cancer cell lines. mRNA expression levels in tumor tissues and cell lines were measured using quantitative real-time PCR, and CASZ1 protein expression in EOC and paired metastatic tumor tissues was analyzed using immunohistochemistry. We found that CASZ1 was highly expressed in EOC tissues and ovarian cancer cell lines and that CASZ1 knockdown suppressed cell migration and invasion in EOC cells. CASZ1a and CASZ1b exerted similar effects on cell migration and invasion in EOC cells. In addition, CASZ1 promoted the epithelial-mesenchymal transition in EOC cells, and CASZ1 knockdown suppressed cancer metastasis in vivo. Furthermore, CASZ1 protein levels were elevated in human metastatic ovarian tumor tissues. Together, these results indicate that CASZ1 is a novel promoter of EOC metastasis and is highly up-regulated in metastatic EOC tumors.
AB - Epithelial ovarian cancer (EOC) carries the highest mortality rate of all gynecologic malignancies. This high mortality rate is attributed to the fact that most cases of ovarian cancer are detected at late stages when metastases are already present. Through microarray analysis, we previously demonstrated that castor zinc finger 1 (CASZ1) is up-regulated in EOC cells. In contrast to its role in EOC, CASZ1 functions a tumor suppressor in neuroblastoma. Human CASZ1 is predominantly expressed in 2 alternatively spliced isoforms: CASZ1a and CASZ1b. In the present study, we investigated the role of CASZ1 in ovarian cancer cell migration and invasion and assessed the value of CASZ1 expression as a prognostic indicator of metastasis in human ovarian cancer. We used a lentivirus expressing CASZ1-shRNA and a plasmid expressing CASZ1 from a CMV promoter to knockdown and overexpress CASZ1, respectively, in the MCAS, RMUG-S, TOV21G, and A2780CP70 ovarian cancer cell lines. mRNA expression levels in tumor tissues and cell lines were measured using quantitative real-time PCR, and CASZ1 protein expression in EOC and paired metastatic tumor tissues was analyzed using immunohistochemistry. We found that CASZ1 was highly expressed in EOC tissues and ovarian cancer cell lines and that CASZ1 knockdown suppressed cell migration and invasion in EOC cells. CASZ1a and CASZ1b exerted similar effects on cell migration and invasion in EOC cells. In addition, CASZ1 promoted the epithelial-mesenchymal transition in EOC cells, and CASZ1 knockdown suppressed cancer metastasis in vivo. Furthermore, CASZ1 protein levels were elevated in human metastatic ovarian tumor tissues. Together, these results indicate that CASZ1 is a novel promoter of EOC metastasis and is highly up-regulated in metastatic EOC tumors.
UR - http://www.scopus.com/inward/record.url?scp=84991525028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991525028&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:84991525028
VL - 6
SP - 1253
EP - 1270
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
SN - 2156-6976
IS - 6
ER -